Spraying living skin cells directly onto the wound was found to heal venous leg ulcers better than standard care, according to the results of a trial published online first in The Lancet on Friday.
The phase 2b clinical trial tested a “spray-on skin” that is under development for the treatment of venous leg ulcers. It contains two types of living, growth-arrested skin cells, keratinocytes and fibroblasts.
The treatment, which is described as an “allogeneic living cell bioformulation” is being developed by Healthpoint Biotherapeutics of Fort Worth, Texas.
The bioformulation, called HP802-247, contains a particular combination of keratinocytes and fibroblasts, which are thought to interact with the patient’s own cells to promote wound healing and tissue regeneration.
Results of previous lab culture experiments suggest they release various growth factors and cytokines into the wound environment, said the company in a statement.
About 2.5 million Americans suffer from leg ulcers, an increasingly common condition where circulation in the lower legs is so poor, usually because of damaged veins or valves or both, that it leads to open wounds or ulcers that are very slow to heal and often recur, developing into chronic non-healing wounds.
The trial, which took place in 28 centers in the US and Canada, tested the effectiveness of two concentrations and dosing frequencies of the treatment when combined with standard care, compared to control plus standard care, in healing venous leg ulcers over a 12-week period.
228 patients were randomly assigned in a double blind manner to receive one of four doses (5·0 x 10 million cells per mL every 7 days or every 14 days, or 0·5 x 10 million cells per mL every 7 days or every 14 days), or the control formulation (vehicle alone every 7 days). (Double blind means neither the patients nor the professionals who administered the treatment knew whether they were using the active agent or the control).
Each patient had up to three venous leg ulcers, with diagnosis confirmed by ultrasound, and with at least one ulcer measuring between 2 and 12 square cm in area, that had persisted for between 4 and 104 weeks.
The primary measure of success was the average change in wound area by the end of week 12.
Overall, the spray-on skin achieved statistically significant improvement, as compared with control plus standard care.
The authors write there was a “significantly greater mean reduction in wound area associated with active treatment”, with the “0·5 x 10 million cells/mL every 14 days showing the largest improvement compared with vehicle”.
The most frequently reported adverse events were skin ulcers, cellulitis, wound infection, and skin irritation. These were much the same in all groups.
The authors conclude that at the appropriate dose, “venous leg ulcers can be healed with a spray formulation of allogeneic neonatal keratinocytes and fibroblasts without the need for tissue engineering”.
In an accompanying commentary, Matthias Augustin, of the University of Hamburg, and Wolfgang Vanscheidt, of Dermatologische Praxisgemeinschafts in Freiberg, Germany, note that:
“In a well-done clinical trial in The Lancet, Robert Kirsner and colleagues have clearly shown that a specific cell therapy for venous leg ulcers can lead to a significantly higher healing rate than for vehicle alone in hard-to-heal [venous] wounds for which compression treatment has been applied unsuccessfully.”
Written by Catharine Paddock PhD